TWI641609B - 一種ｊａｋ激酶抑制劑的硫酸氫鹽及其製備方法 - Google Patents

一種ｊａｋ激酶抑制劑的硫酸氫鹽及其製備方法 Download PDF

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Publication number: TWI641609B
Authority: TW; Taiwan
Prior art keywords: pyrrole; preparation; hexahydrocyclopenta; pyrrolo; methyl
Prior art date: 2013-06-07

Application number

TW103116955A

Other languages

English (en)

Chinese (zh)

Other versions

TW201514180A (zh

Inventor

孫飄揚

Piaoyang Sun

武乖利

Guaili Wu

高曉暉

Xiaohui GAO

沈靈佳

Lingjia SHEN

Original Assignee

江蘇恆瑞醫藥股份有限公司

Jiangsu Hengrui Medicine Co., Ltd.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2013-06-07

Filing date

2014-05-14

Publication date

2018-11-21

2014-05-14 Application filed by 江蘇恆瑞醫藥股份有限公司, Jiangsu Hengrui Medicine Co., Ltd. filed Critical 江蘇恆瑞醫藥股份有限公司

2015-04-16 Publication of TW201514180A publication Critical patent/TW201514180A/zh

2018-11-21 Application granted granted Critical

2018-11-21 Publication of TWI641609B publication Critical patent/TWI641609B/zh

Links

QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title claims abstract description 20
238000002360 preparation method Methods 0.000 title claims abstract description 14
229940043355 kinase inhibitor Drugs 0.000 title abstract description 8
239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 8
-1 3-methoxy-1,2,4-thiadiazol-5-yl Chemical group 0.000 claims abstract description 32
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
150000001875 compounds Chemical class 0.000 claims description 21
238000006243 chemical reaction Methods 0.000 claims description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 14
229940079593 drug Drugs 0.000 claims description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
239000002904 solvent Substances 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
150000001298 alcohols Chemical class 0.000 claims description 2
150000001350 alkyl halides Chemical class 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000011259 mixed solution Substances 0.000 claims description 2
239000012046 mixed solvent Substances 0.000 claims description 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
230000035484 reaction time Effects 0.000 claims description 2
ZAEUOCGSFKFWHY-UHFFFAOYSA-N 3-methoxy-1,2,4-thiadiazole Chemical compound COC=1N=CSN=1 ZAEUOCGSFKFWHY-UHFFFAOYSA-N 0.000 claims 1
238000005755 formation reaction Methods 0.000 claims 1
239000000243 solution Substances 0.000 description 13
108010024121 Janus Kinases Proteins 0.000 description 9
102000015617 Janus Kinases Human genes 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 7
229960001350 tofacitinib Drugs 0.000 description 7
UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 5
239000004012 Tofacitinib Substances 0.000 description 5
229960000485 methotrexate Drugs 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000000034 method Methods 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000036267 drug metabolism Effects 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
241000282560 Macaca mulatta Species 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
206010003246 arthritis Diseases 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
210000001503 joint Anatomy 0.000 description 2
239000013557 residual solvent Substances 0.000 description 2
230000011664 signaling Effects 0.000 description 2
OJCCUUWVUOCZAA-UHFFFAOYSA-N 3-methoxy-1,2,4-thiadiazol-5-amine Chemical compound COC1=NSC(N)=N1 OJCCUUWVUOCZAA-UHFFFAOYSA-N 0.000 description 1
BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
108010008165 Etanercept Proteins 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
229940116839 Janus kinase 1 inhibitor Drugs 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000010100 anticoagulation Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000010250 cytokine signaling pathway Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000003480 eluent Substances 0.000 description 1
229940073621 enbrel Drugs 0.000 description 1
210000003191 femoral vein Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229940048921 humira Drugs 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000003960 inflammatory cascade Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
239000000203 mixture Substances 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
210000002997 osteoclast Anatomy 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
238000009522 phase III clinical trial Methods 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
WLFZBSSDZNVOJT-UHFFFAOYSA-N phenyl n-(3-methoxy-1,2,4-thiadiazol-5-yl)carbamate Chemical compound COC1=NSC(NC(=O)OC=2C=CC=CC=2)=N1 WLFZBSSDZNVOJT-UHFFFAOYSA-N 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
229940116176 remicade Drugs 0.000 description 1
238000011160 research Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
238000009097 single-agent therapy Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
210000005222 synovial tissue Anatomy 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
231100000925 very toxic Toxicity 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Rheumatology (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

TW103116955A 2013-06-07 2014-05-14 一種ｊａｋ激酶抑制劑的硫酸氫鹽及其製備方法 TWI641609B (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CN201310227683		2013-06-07
??201310227683.X		2013-06-07

Publications (2)

Publication Number	Publication Date
TW201514180A TW201514180A (zh)	2015-04-16
TWI641609B true TWI641609B (zh)	2018-11-21

Family

ID=52007520

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW103116955A TWI641609B (zh)	2013-06-07	2014-05-14	一種ｊａｋ激酶抑制劑的硫酸氫鹽及其製備方法

Country Status (15)

Country	Link
US (1)	US9422300B2 (fr)
EP (1)	EP3006445B1 (fr)
JP (1)	JP6323885B2 (fr)
KR (1)	KR102275326B1 (fr)
CN (1)	CN104470927B (fr)
AU (1)	AU2014277506B2 (fr)
BR (1)	BR112015029463B1 (fr)
CA (1)	CA2913194C (fr)
ES (1)	ES2655074T3 (fr)
HU (1)	HUE036533T2 (fr)
MX (1)	MX372932B (fr)
PT (1)	PT3006445T (fr)
RU (1)	RU2665680C2 (fr)
TW (1)	TWI641609B (fr)
WO (1)	WO2014194741A1 (fr)

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* Cited by examiner, † Cited by third party
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CN105566327A (zh) *	2014-10-09	2016-05-11	江苏恒瑞医药股份有限公司	一种jak激酶抑制剂的硫酸氢盐的i型结晶及其制备方法
WO2016070697A1 (fr) *	2014-11-05	2016-05-12	江苏恒瑞医药股份有限公司	Forme cristalline de bisulfate inhibiteur de kinase jak et procédé de préparation correspondant
CA3014090A1 (fr) *	2016-02-19	2017-08-24	Jiangsu Hengrui Medicine Co., Ltd.	Composition pharmaceutique contenant un inhibiteur de janus kinase (jak) ou un sel pharmaceutiquement acceptable de celui-ci
KR20190084299A (ko) *	2016-11-23	2019-07-16	지앙수 헨그루이 메디슨 컴퍼니 리미티드	피롤로 6-원 헤테로방향족 고리 유도체의 제조 방법 및 그의 중간체
TW201827436A (zh) *	2017-01-20	2018-08-01	大陸商江蘇恆瑞醫藥股份有限公司	一種ｊａｋ激酶抑制劑的硫酸氫鹽的晶型及其製備方法
WO2019096303A1 (fr) *	2017-11-20	2019-05-23	江苏恒瑞医药股份有限公司	Composition pharmaceutique pour administration topique et procédé de préparation associé
BR112021008742A2 (pt) *	2018-11-05	2021-08-10	Avista Pharma Solutions, Inc.	compostos químicos
CN111205290B (zh) *	2018-11-22	2021-10-08	江苏恒瑞医药股份有限公司	一种jak激酶抑制剂的结晶形式及其制备方法
CN111440127B (zh) *	2019-01-17	2022-07-26	青岛农业大学	一种噻唑酰胺类化合物及其制备和应用
US12528811B2 (en)	2019-09-05	2026-01-20	Universität Bern	Substituted cyclopenta[2,1-b:5,1-bâ€™]dipyrroles as Janus kinase (JAK) inhibitors
CN113698404B (zh) *	2020-05-21	2023-06-16	江苏恒瑞医药股份有限公司	一种低溶剂残留的六氢环戊并[c]吡咯-2(1H)-甲酰胺化合物及其制备方法
WO2022027041A1 (fr)	2020-07-28	2022-02-03	Arcutis Biotherapeutics, Inc.	Formulation topique contenant un inhibiteur de jak et le laureth-4
MX2023005763A (es)	2020-11-17	2023-05-29	Arcutis Biotherapeutics Inc	Composiciones y metodos para la administracion dermica profunda de farmacos.
CN112457272B (zh) *	2020-12-02	2022-04-19	上海再启生物技术有限公司	(3-甲氧基-1,2,4-噻二唑-5-氨基)甲酸苯酯的制备方法
CN118632687A (zh)	2021-11-11	2024-09-10	阿尔库缇斯生物疗法股份有限公司	用于深层皮肤药物递送的螺内酯药物组合物
CA3240662A1 (fr)	2021-12-15	2023-06-22	Herbert R. Brinkman	Formulations de shr0302 stables
CN120641104A (zh) *	2023-02-07	2025-09-12	瑞石生物医药有限公司	一种局部给药的药物组合物、其制备方法及应用
KR20250085523A (ko)	2023-12-05	2025-06-12	김동균	광섬유를 사용한 스마트 팜 식물성장 조명 최적화 시스템
WO2026050923A1 (fr) *	2024-09-04	2026-03-12	上海再启生物技术有限公司	Procédé de synthèse d'un intermédiaire clé d'inhibiteur de kinase jak
CN119907789B (zh) *	2024-09-06	2025-11-18	上海再启生物技术有限公司	一种jak激酶抑制剂关键中间体的制备方法

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- 2014-05-05 JP JP2016517135A patent/JP6323885B2/ja active Active
- 2014-05-05 HU HUE14807030A patent/HUE036533T2/hu unknown
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- 2014-05-05 AU AU2014277506A patent/AU2014277506B2/en active Active
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- 2014-05-05 CA CA2913194A patent/CA2913194C/fr active Active
- 2014-05-05 EP EP14807030.3A patent/EP3006445B1/fr active Active
- 2014-05-05 MX MX2015016513A patent/MX372932B/es active IP Right Grant
- 2014-05-05 CN CN201480001854.XA patent/CN104470927B/zh active Active
- 2014-05-05 WO PCT/CN2014/076794 patent/WO2014194741A1/fr not_active Ceased
- 2014-05-05 RU RU2015156142A patent/RU2665680C2/ru active
- 2014-05-05 ES ES14807030.3T patent/ES2655074T3/es active Active
- 2014-05-05 US US14/895,117 patent/US9422300B2/en active Active
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Publication number	Publication date
CA2913194A1 (fr)	2014-12-11
EP3006445A1 (fr)	2016-04-13
KR102275326B1 (ko)	2021-07-12
RU2015156142A (ru)	2017-07-17
EP3006445A4 (fr)	2016-11-23
MX2015016513A (es)	2016-04-15
HUE036533T2 (hu)	2018-07-30
CN104470927A (zh)	2015-03-25
CN104470927B (zh)	2016-05-04
JP6323885B2 (ja)	2018-05-16
BR112015029463B1 (pt)	2023-01-10
BR112015029463A2 (pt)	2017-07-25
AU2014277506B2 (en)	2017-08-31
KR20160032021A (ko)	2016-03-23
MX372932B (es)	2020-03-23
WO2014194741A1 (fr)	2014-12-11
HK1206026A1 (zh)	2015-12-31
ES2655074T3 (es)	2018-02-16
US20160102098A1 (en)	2016-04-14
JP2016520134A (ja)	2016-07-11
EP3006445B1 (fr)	2017-11-15
CA2913194C (fr)	2021-03-02
RU2665680C2 (ru)	2018-09-04
AU2014277506A1 (en)	2016-01-21
TW201514180A (zh)	2015-04-16
US9422300B2 (en)	2016-08-23
RU2015156142A3 (fr)	2018-03-19
PT3006445T (pt)	2018-01-09

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